Endocrine physiology

Question 1

What are some examples of peptide hormones?

Answer 1

Oxytocin, insulin, glucagon, FSH, LH, GH, PTH, ADH, etc.

Question 2

2. Describe the characteristics of peptide hormones.

Answer 2

• Water soluble<br></br>- Have a hydrophilic amino acid<br></br>- Do not precipitate<br></br>- Do not pass freely through the cell membrane (phospholipid bilayer)<br></br>- Relatively big size<br></br>- Charged<br></br>- Require a receptor on the cell membrane<br></br>- Utilizes the 2nd Messenger Systems (Gs, Gq, Gi)

Question 3

3. Name some examples of steroid hormones.

Answer 3

Testosterone, estrogen, progesterone, aldosterone, cortisol, gonadocorticoids, etc.

Question 4

4. What are the characteristics of steroid hormones?

Answer 4

Lipid soluble<br></br>- Derived from cholesterol<br></br>- Pass through the phospholipid barrier<br></br>- Bind to receptors inside the cell

Question 5

5. What distinguishes the interaction of peptide and steroid hormones with cells?

Answer 5

Peptide hormones interact with cell membrane receptors and utilize 2nd Messenger Systems, while steroid hormones bind to receptors inside the cell.

Question 6

6. How is the structure of GPCR characterized?

Answer 6

• Receptor with seven transmembrane helices<br></br>- Structure protein passes through the membrane 7 times<br></br>- Also known as seven pass transmembrane receptors or ‘serpentine’ receptors<br></br>- Ligand binding sites are found in extracellular regions or between helices<br></br>- Has an intracellular binding site for the G protein

Question 7

7. What is the typical state of the G protein in its inactive form?

Answer 7

The G protein is normally bound to GDP.

Question 8

8. Describe the process of GPCR activation.

Answer 8

• Binding of a peptide hormone changes the overall three-dimensional structure of the receptor<br></br>- The receptor activates the G protein by removing GDP and adding on GTP<br></br>- The activated G protein can move along the membrane as it is a peripheral membrane protein<br></br>- ‘Off’ state is when the G protein is bound to GDP<br></br>- ‘On’ state is when GDP is removed and GTP is added

Question 9

9. What are the characteristics of Gs protein-coupled receptors?

Answer 9

• Involvement of G stimulatory protein (Gs protein)<br></br>- Activated Gs protein goes to an effector enzyme on the cell membrane, Adenylate cyclase<br></br>- The effector enzyme becomes very active

Question 10

10. What is the role of Adenylate cyclase in the Gs protein-coupled receptor pathway?

Answer 10

Adenylate cyclase has a specific enzyme, GTPase<br></br>- GTPase cuts the GTP, turning it into GDP (removes a phosphate)<br></br>- G protein is turned off<br></br>- Energy is produced and used to convert ATP to cAMP<br></br>- cAMP activates protein kinase A (pkA)

Question 11

11. What can the activated pkA phosphorylate, leading to various effects?

Answer 11

The activated pkA can phosphorylate multiple proteins, resulting in different effects, including:<br></br>- Regulation of membrane permeability for different ions (Phosphorylation of channel proteins on the cell membrane)<br></br>- Regulation of metabolic pathways (glycolysis) (Phosphorylation of enzymes)<br></br>- Increased production of new proteins (transcription) (Phosphorylation of transcription factor)<br></br>- Increased cell proliferation and DNA replication, etc.

Question 12

12. How does pkA regulate membrane permeability for different ions?

Answer 12

By phosphorylating channel proteins on the cell membrane.

Question 13

13. In what way does pkA regulate metabolic pathways such as glycolysis?

Answer 13

By phosphorylating enzymes involved in metabolic pathways.

Question 14

14. How does pkA contribute to increased production of new proteins through transcription?

Answer 14

By phosphorylating transcription factors.

Question 15

15. What effects does pkA have on cell proliferation and DNA replication?

Answer 15

pkA’s activity leads to increased cell proliferation and DNA replication.

Question 16

16. How does the activated Gq protein initiate signaling in the cell membrane?

Answer 16

• The activated Gq protein goes to an effector enzyme on the cell membrane, Phospholipase C<br></br>- The effector enzyme becomes very active

Question 17

17. What is the role of Phospholipase C in the Gq protein-coupled receptor pathway?

Answer 17

• Phospholipase C has a specific enzyme, GTPase<br></br>- GTPase cuts the GTP and turns it into GDP, turning off the G protein<br></br>- Energy is produced and used to cut phosphatidylinositol biphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3)<br></br>- DAG activates protein kinase C (pkC) which shares similar functions with pkA (phosphorylation of different proteins)

Question 18

18. What is the role of IP3 in the Gq protein-coupled receptor pathway?

Answer 18

• IP3 affects the smooth endoplasmic reticulum or the sarcoplasmic reticulum in muscle cells<br></br>- Binds to specific receptors on the reticulum, opening a channel<br></br>- Calcium (Ca++) leaves the reticulum and enters the cytoplasm

Question 19

19. How does Calcium (Ca++) further signal in the cell?

Answer 19

• Calcium binds to Calmodulin<br></br>- Activated Calmodulin activates different types of kinases<br></br>- The activated kinases phosphorylate different proteins, such as myosin to initiate contractions

Question 20

20. Describe the mechanism by which oxytocin increases calcium levels inside the cell.

Answer 20

Oxytocin utilizes the Gq protein-coupled receptor pathway:<br></br>- Gq protein activates Phospholipase C<br></br>- Phospholipase C generates IP3 and DAG<br></br>- IP3 opens calcium channels on the smooth endoplasmic reticulum<br></br>- Calcium leaves the reticulum and binds to Calmodulin<br></br>- Activated Calmodulin activates kinases, leading to increased calcium levels and muscle contractions.

Question 21

21. Where can steroid hormone receptors be located?

Answer 21

Steroid hormone receptors can be either intracytosolic or intranuclear.

Question 22

22. What is the typical state of steroid hormone receptors in the ‘Off’ state?

Answer 22

Normally bound to heat shock protein (HSP)<br></br>- This state prevents their activation.

Question 23

23. Describe the process of activation for steroid hormone receptors.

Answer 23

• When a steroid hormone (e.g., testosterone) goes through the cell membrane, it displaces the heat shock protein (HSP), leading to the activation of the receptor.<br></br>- This transition signifies the ‘On’ state of the receptor.

Question 24

24. What happens in the ‘On’ state of steroid hormone receptors?

Answer 24

• The activated receptor binds to a specific gene sequence called the hormone response element (HRE).<br></br>- This interaction triggers a variety of effects, including DNA replication, cell proliferation (mitosis), transcription followed by translation, and the synthesis of proteins controlling metabolism, ion permeability, protein synthesis, and cell growth.

Question 25

25. How does the enzyme phosphodiesterase (PDE) function in cellular pathways?

Answer 25

Phosphodiesterase (PDE) breaks down cAMP or Phospholipase C to prevent these pathways from continuously occurring.

Question 26

26. What is the purpose of inhibiting cAMP or Phospholipase C pathways?

Answer 26

Inhibition by phosphodiesterase prevents prolonged activation of these pathways, regulating the duration and intensity of cellular responses mediated by cAMP or Phospholipase C.

Question 27

27. How does phosphodiesterase influence cAMP and Phospholipase C pathways?

Answer 27

Phosphodiesterase breaks down cAMP or Phospholipase C into inactive components, terminating the signaling cascades they initiate.

Question 28

28. What is the role of phosphodiesterase in cellular regulation?

Answer 28

Phosphodiesterase plays a crucial role in maintaining cellular homeostasis by preventing continuous and uncontrolled activation of signaling pathways, ensuring a balanced and regulated cellular response.